Potentiation of receptor-mediated cAMP production: role in the cross-talk between vasopressin V1a and V2 receptor transduction pathways.
Cross-talk between the phospholipase C and adenylyl cyclase signalling pathways was investigated in Chinese hamster ovary (CHO) cells transfected with the V1a and V2 vasopressin receptors. Cell lines expressing V1a, V2, or both V1a and V2 receptors, were established and characterized. Stimulation of V2 receptors by vasopressin induced a dose-dependent increase in cAMP accumulation, whereas stimulation of V1a receptor resulted in an increase in intracellular calcium without any change in basal cAMP. The simultaneous stimulation of V2 and V1a receptors by vasopressin elicited an intracellular cAMP accumulation which was twice that induced by stimulation of V2 receptor alone with deamino-[d-Arg8]vasopressin. This potentiation between V1a and V2 receptors was mimicked by activation of protein kinase C (PKC) with PMA, and was suppressed when PKC activity was inhibited by bisindolylmaleimide. The potentiation was observed in the presence or absence of 1 mM 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, implying that an alteration in cAMP hydrolysis was not involved. Vasopressin, as well as PMA, had no effect on the forskolin-induced cAMP accumulation, suggesting that PKC did not directly stimulate the cyclase activity. On the other hand, vasopressin, like PMA, potentiated the cAMP accumulation induced by cholera toxin, an activator of Galphas protein. These results suggest that, in CHO cells, vasopressin V1a receptor potentiates the cAMP accumulation induced by the V2 receptor through a PKC-dependent increase in the coupling between Gs protein and adenylyl cyclase.
Klingler
C
C
Service de Biologie Cellulaire, CEA, Centre d'Etudes de Saclay, Gif-sur-Yvette, 91191 Cedex, France.
Ancellin
N
N
Barrault
M B
MB
Morel
A
A
Corman
B
B
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis*; D003894:Deamino Arginine Vasopressin / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D002772:Cholera Toxin; D000242:Cyclic AMP; D011493:Protein Kinase C; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D003894:Deamino Arginine Vasopressin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine